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In climatically suitable regions across Europe, vineyards can be the dominant perennial crop type. While many wine-growing landscapes are intensively managed, they may still be an attractive habitat for a wide range of bird species. In this study we investigated how breeding birds in three wine-growing regions in Europe (Germany: Palatinate, France: Bordeaux, Austria: Leithaberg) are influenced by the composition of the landscape, focussing on woody semi-natural vegetation.We recorded bird vocalizations with autonomous sound recorders in 93 landscapes across Europe. Bird species were identified according to their songs and calls. The landscape in a 200-m buffer around the recording points was mapped. In total, we recorded 72 bird species, including species typical for vineyard landscapes such as cirl bunting (Emberiza cirlus), hoopoe (Upupa epops) and turtle dove (Streptopelia turtur). For all three countries we found that an increase in overall woody vegetation in the landscape led to an increase in species richness and altered community composition. Most species were recorded in landscapes with abundant hedges, small woods and tree rows rather than in vineyard-dominated landscapes but e.g. woodlark (Lullula arborea) and linnet (Linaria cannabina) showed an opposite preference.We conclude that in intensively used wine-growing landscapes the ongoing decline in farmland birds and the ecosystem services they provide can be reversed by the reintroduction of semi-natural woody vegetation between vineyards. These in frequently many cases linear structural elements can be established included in the landscape with only small losses in production area.

Background: Hepatocellular carcinoma (HCC) accounts for approximately 90% of liver cancer cases. Sorafenib, the first drug to demonstrate survival benefits for advanced HCC, was validated through the SHARP randomized clinical trial (RCT). While RCTs are essential for assessing new therapies, real-world studies provide additional insights into their effectiveness in routine clinical practice. This study aimed to evaluate sorafenib’s real-world effectiveness by analyzing overall survival (OS) and the time to radiological and symptomatic progression. Methods: Data from 368 patients treated with sorafenib at a Brazilian Cancer Center between 2009 and 2020 were retrospectively reviewed. Results: The median OS was 9.6 months, and the time to radiological progression was 5.3 months, similar to the SHARP trial. However, the time to symptomatic progression was shorter (2.3 months) than the SHARP study (4.1 months). In terms of safety, 27.4% of patients presented clinically relevant toxicities, and 24.5% needed to discontinue treatment due to toxicity. Conclusions: Overall, sorafenib demonstrated effectiveness in the studied population, with OS and radiological progression times comparable to SHARP study results. The difference in symptomatic progression may be due to the study’s retrospective nature and limitations.

Infection of airway epithelial cells with severe acute respiratory coronavirus 2 (SARS-CoV-2) can lead to severe respiratory tract damage and lung injury with hypoxia. It is challenging to sample the lower airways non-invasively and the capability to identify a highly representative specimen that can be collected in a non-invasive way would provide opportunities to investigate metabolomic consequences of COVID-19 disease. In the present study, we performed a targeted metabolomic approach using liquid chromatography coupled with high resolution chromatography (LC-MS) on exhaled breath condensate (EBC) collected from hospitalized COVID-19 patients (COVID+) and negative controls, both non-hospitalized and hospitalized for other reasons (COVID-). We were able to noninvasively identify and quantify inflammatory oxylipin shifts and dysregulation that may ultimately be used to monitor COVID-19 disease progression or severity and response to therapy. We also expected EBC-based biochemical oxylipin changes associated with COVID-19 host response to infection. The results indicated ten targeted oxylipins showing significative differences between SAR-CoV-2 infected EBC samples and negative control subjects. These compounds were prostaglandins A2 and D2, LXA4, 5-HETE, 12-HETE, 15-HETE, 5-HEPE, 9-HODE, 13-oxoODE and 19(20)-EpDPA, which are associated with specific pathways (i.e. P450, COX, 15-LOX) related to inflammatory and oxidative stress processes. Moreover, all these compounds were up-regulated by COVID+, meaning their concentrations were higher in subjects with SAR-CoV-2 infection. Given that many COVID-19 symptoms are inflammatory in nature, this is interesting insight into the pathophysiology of the disease. Breath monitoring of these and other EBC metabolites presents an interesting opportunity to monitor key indicators of disease progression and severity.

Abstract The red-legged partridge (Alectoris rufa) is a popular game bird species that is in decline in several regions of southwestern Europe. The introduction of farm-reared individuals of a distinct genetic make-up in hunting reserves can result in genetic swamping of wild populations. Here we present a de novo genome assembly for the red-legged partridge based on long-read sequencing technology. The assembled genome size is 1.14 Gb, with scaffold N50 of 37.6 Mb and contig N50 of 29.5 Mb. Our genome is highly contiguous and contains 97.06% of complete avian core genes. Overall, the quality of this genome assembly is equivalent to those available for other close relatives such as the Japanese quail or the chicken. This genome assembly will contribute to the understanding of genetic dynamics of wild populations of red-legged partridges with releases of farm-reared reinforcements and to appropriate management decisions of such populations.

Abstract The red-legged partridge Alectoris rufa plays a crucial role in the ecosystem of southwestern Europe, and understanding its genetics is vital for conservation and management. Here we sequence, assemble, and annotate a highly contiguous and nearly complete version of its genome. This assembly encompasses 96.9% of the avian genes flagged as essential in the BUSCO aves_odb10 dataset. Moreover, we pinpointed RNA and protein-coding genes, 95% of which had functional annotations. Notably, we observed significant chromosome rearrangements in comparison to quail (Coturnix japonica) and chicken (Gallus gallus). In addition, a comparative phylogenetic analysis of these genomes suggests that A. rufa and C. japonica diverged roughly 20 million years ago and that their common ancestor diverged from G. gallus 35 million years ago. Our assembly represents a significant advancement towards a complete reference genome for A. rufa, facilitating comparative avian genomics, and providing a valuable resource for future research and conservation efforts for the red-legged partridge.

Abstract Background It has been suggested that maternal satisfaction should be included as an additional and appropriate outcome indicator in relation to the breastfeeding process. The aim of this study was to analyze the psychometric properties of various existing versions of the Maternal Breastfeeding Evaluation Scale in a Spanish sample. Methods This was a longitudinal observational study, evaluated at three different time points: in the hospital after delivery, and then at five and 12 months after delivery in a Spanish sample. A total of 690 mother participated in this study. Results Confirmatory factor analysis results indicated an improved fit of the data to the original model (CFI = 0.984; TLI = 0.982; RMSEA = 0.079). All dimensions of the Maternal Breastfeeding Evaluation Scale are positively associated with breastfeeding rates and negatively associated with perceived difficulty in continuing to breastfeed after returning to work at five months postpartum. Moreover, the scale can predict breastfeeding behavior at 12 months postpartum. Conclusions The results of this study indicate that the structure of the original version of the Maternal Breastfeeding Evaluation Scale mean it is a is valid and reliable tool for assessing maternal perceptions of the breastfeeding experience in Spain. This research enhances our understanding of maternal satisfaction with the breastfeeding experience and its potential implications for supporting breastfeeding practices. It is an opportunity for the academic, healthcare, and policy sectors to develop more effective interventions to improve breastfeeding rates and ensure a positive experience for mothers.

BackgroundDespite decades of research on predictors of extubation success, use of ventilatory support after extubation is common and 10-20% of patients require re-intubation. Proportional assist ventilation (PAV) mode automatically calculates estimated total work of breathing (total WOB). Here, we assessed the performance of total WOB to predict extubation failure in invasively ventilated subjects.MethodsThis prospective observational study was conducted in 6 adult ICUs at an academic medical center. We enrolled intubated subjects who successfully completed a spontaneous breathing trial, had a rapid shallow breathing index < 105 breaths/min/L, and were deemed ready for extubation by the primary team. Total WOB values were recorded at the end of a 30-min PAV trial. Extubation failure was defined as any respiratory support and/or re-intubation within 72 h of extubation. We compared total WOB scores between groups and performance of total WOB for predicting extubation failure with receiver operating characteristic curves.ResultsOf 61 subjects enrolled, 9.8% (n = 6) required re-intubation, and 50.8% (n = 31) required any respiratory support within 72 h of extubation. Median total WOB at 30 min on PAV was 0.9 J/L (interquartile range 0.7-1.3 J/L). Total WOB was significantly different between subjects who failed or were successfully extubated (median 1.1 J/L vs 0.7 J/L, P = .004). The area under the curve was 0.71 [95% CI 0.58-0.85] for predicting any requirement of respiratory support and 0.85 [95% CI 0.69-1.00] for predicting re-intubation alone within 72 h of extubation. Total WOB cutoff values maximizing sensitivity and specificity equally were 1.0 J/L for any respiratory support (positive predictive value [PPV] 70.0%, negative predictive value [NPV] 67.7%) and 1.3 J/L for re-intubation (PPV 26.3%, NPV 97.6%).ConclusionsThe discriminative performance of a PAV-derived total WOB value to predict extubation failure was good, indicating total WOB may represent an adjunctive tool for assessing extubation readiness. However, these results should be interpreted as preliminary, with specific thresholds of PAV-derived total WOB requiring further investigation in a large multi-center study.

Background: The objective of this study was to evaluate the use of telomere length measurements as diagnostic biomarkers during early screening for lung cancer in high-risk patients. Methods: This was a prospective study of patients undergoing lung cancer diagnosis at two Spanish hospitals between April 2017 and January 2020. Telomeres from peripheral blood lymphocytes were analysed by Telomere Analysis Technology, which is based in high-throughput quantitative fluorescent in situ hybridization. Analytical predictive models were developed using Random Forest from the dataset of telomere-associated variables (TAV). Receiver Operating Characteristic curves were used to characterize model performance. Findings: From 233 patients undergoing lung cancer diagnosis, 106 patients aged 55–75 with lung cancer or lung cancer and COPD were selected. A control group (N = 453) included individuals of similar age with COPD or healthy. Telomere analysis showed that patients in the cancer cohort had a higher proportion of short telomeres compared to the control cohort. A TAV-based predictive model assuming a prevalence of 5 % of lung cancer among screened subjects showed an AUC of 0.98 %, a positive predictive value of 0.60 (95 % CI, 0.49–0.70) and a negative predictive value of 0.99 (95 % CI, 0.98–0.99) for prediction of lung cancer. Interpretation: The results of this study suggest that TAV analysis in peripheral lymphocytes can be considered a useful diagnostic tool during screening for lung cancer in high-risk patients. TAV-based models could improve the predictive power of current initial diagnostic pathways, but further work is needed to integrate them into routine clinical evaluation. Funding: Life Length SL.

Background Becoming a mother is a very important process because of the impact it can have on women and their families. Currently, there is no validated questionnaire that evaluates the process of becoming a mother in the Spanish population. Moreover, no consistent results have been obtained to identify significant differences between primiparous and multiparous mothers. Aim (1) Linguistic and metric validation of the Being a Mother scale (BaM-13) in the Spanish population, (2) analysis of possible differences between primiparous and multiparous mothers’ experience of motherhood. Methods Instrumental design. In 2016–2017, a sample of 579 mothers with children between 6 and 11 months of age completed the Spanish version of BaM-13. The instrument was translated using forward and back translation. Construct validity, internal consistency, and criterion validity were empirically analyzed. Results Factorial analyses showed that the scale presented two adequate factors. Internal consistency of the global scale (α = 0.818, ω = 0.861), the Postnatal bonding factor (α = 0.773, ω = 0.784), and the Adult’s experience factor (α = 0.710, ω = 0.721) was adequate. Significant associations were found with postpartum depression (r = 0.560), parental competence (r = − 0.584) and postnatal bonding (r = − 0.327). In terms of parity, primiparous mothers have greater difficulty in postnatal bonding, compared to multiparous mothers (p = 0.006). Conclusions The Spanish version of the BaM-13 scale is valid for measuring mothers’ experience of motherhood in a wide range of domains. The findings of the study show the importance of considering parity in the experience of becoming a mother, highlighting the approach to postnatal bonding in primiparous mothers. Additionally, we underline that it should not be assumed that multiparous mothers experience fewer difficulties in their motherhood process.

BackgroundAn urgent need exists to rapidly screen potential therapeutics for severe COVID-19 or other emerging pathogens associated with high morbidity and mortality.MethodsUsing an adaptive platform design created to rapidly evaluate investigational agents, hospitalised patients with severe COVID-19 requiring ≥6 L/min oxygen were randomised to either a backbone regimen of dexamethasone and remdesivir alone (controls) or backbone plus one open-label investigational agent. Patients were enrolled to the arms described between July 30, 2020 and June 11, 2021 in 20 medical centres in the United States. The platform contained up to four potentially available investigational agents and controls available for randomisation during a single time-period. The two primary endpoints were time-to-recovery (

Abstract Background In non-endemic countries, malaria can be transmitted through blood donations from imported cases. To ensure standards of quality and safety of human blood, the European Union and Spanish national law, requires a deferral period, or a screening by immunological or genomic test among those donors with potential risk of malaria. Scientific societies, European Committee on Blood Transfusion, and Spanish Society of Haematology and Haemotherapy, refer only to the result of the immunological test. Methods An observational retrospective study was performed in potential donors with a positive immunological test for malaria done in the Regional Transfusion Center in Madrid and referred to the National Reference Unit for Tropical Diseases in Madrid between 2015–2020. At consultation a Polymerase Chain Reaction (PCR) for malaria was performed. Results During the study period, 121 possible donors attended for consultation at NRU-Trop. Median age: 38.5 (IQR:33–48); median time to consultation was 32 months (IQR:12.5–110). Eighty-two (67.8%) donors were migrants and thirty-nine were travellers (32.2%). ELISA values were available for 109 subjects (90.1%), 56 individual left malaria endemic area > 3 years before. All donors tested negative for Plasmodium spp PCR test (n = 121, 100%). Conclusions None of the subjects with a positive immunologic test deferred as blood donors had a positive genomic test. The presence of Plasmodium spp in collected blood was not detected by molecular techniques. To avoid the loss of potential blood donors, especially those with low incidence red blood cell antigens, as more precise microbiology techniques become available, updating the existing legislation becomes necessary to increase the availability of donated blood.

Abstract Mutations in chromatin regulators are widespread in cancer. Among them, the histone H3 lysine 27 methyltransferase Polycomb Repressive Complex 2 (PRC2) shows distinct alterations according to tumor type. This specificity is poorly understood. Here, we model several PRC2 alterations in one isogenic system to reveal their comparative effects. Focusing then on lymphoma-associated EZH2 mutations, we show that Ezh2 Y641F induces aberrant H3K27 methylation patterns even without wild-type Ezh2, which are alleviated by partial PRC2 inhibition. Remarkably, Ezh2 Y641F rewires the response to PRC2 inhibition, leading to induction of antigen presentation genes. Using a unique longitudinal follicular lymphoma cohort, we further link EZH2 status to abnormal H3K27 methylation. We also uncover unexpected variability in the mutational landscape of successive biopsies, pointing to frequent co-existence of different clones and cautioning against stratifying patients based on single sampling. Our results clarify how oncogenic PRC2 mutations disrupt chromatin and transcription, and the therapeutic vulnerabilities this creates.

Objective As the world faces an aging population, the complexities of care management become increasingly pronounced. While technological solutions hold promise in addressing the dynamic demands of care, many nuances are to be considered in the design and implementation of active and assisted living technologies (AAL) for older adult care. This qualitative study, set in southern Spain, is positioned at the crossroads of healthcare challenges, as seen by the different actors involved in the care process and the technological solutions developed in response to these challenges. By investigating the complex landscape of caregiving and by examining the experiences and challenges faced by caregivers, healthcare professionals, and older adults, we aim to guide the development of vision-based AAL technologies that are responsive to the genuine needs of older adults and those requiring care. Methods A qualitative research methodology was used in the study. In total15 in-depth interviews and five focus groups were conducted with a diverse group of stakeholders involved in the process of care provision and reception. Results While the results demonstrate that there is a readiness for technological solutions, concerns over privacy and trust highlight the need for a carefully integrated, human-centric approach to technology in caregiving. Conclusion This research serves as a compass, guiding future discussions on the intersection of aging, technology, and care, with the ultimate goal of transforming caregiving into a collaborative and enriching journey for all stakeholders involved.

Exhaled breath condensate (EBC) is routinely collected and analyzed in breath research. Because it contains aerosol droplets, EBC samples from SARS-CoV-2 infected individuals harbor the virus and pose the threat of infectious exposure. We report for the first time a safe and consistent method to fully inactivate SARS-CoV-2 in EBC samples and make EBC samples safe for processing and analysis. EBC samples containing infectious SARS-CoV-2 were treated with several concentrations of acetonitrile. The most commonly used 10% acetonitrile treatment for EBC processing failed to completely inactivate the virus in samples and viable virus was detected by the assay of SARS-CoV-2 infection of Vero E6 cells in a biosafety level 3 laboratory. Treatment with either 50% or 90% acetonitrile was effective to completely inactivate the virus, resulting in safe, non-infectious EBC samples that can be used for metabolomic analysis. Our study provides SARS-CoV-2 inactivation protocol for the collection and processing of EBC samples in the clinical setting and for advancing to metabolic assessments in health and disease.

Foundation: the lack of physical activity is linked to high levels of sedentary behavior, which constitutes an important risk factor for the development of chronic diseases such as: overweight and obesity, which in adolescents has become a health problem worldwide. Objective: to determine the level of physical activity of the students of the secondary level of a public school in Lima. Method: a descriptive and cross-sectional study was carried out in which students between the ages of 12 and 17 enrolled in the 2019 school year were included. The population consisted of 470 high school students from the Institución Educativa Simón Bolívar school in the Palomino Urbanization of Cercado de Lima. The Inventory of Habitual Physical Activity for Adolescents and the eating behaviors module of the World Health Survey of Schoolchildren were applied. Simple random probabilistic sampling was used. Results: 52.3 % of the patients were male, the most frequent age range was 13 to 15 years with 70.1 %. Most presented a normal nutritional status (83.3 %). The level of habitual physical activity was mostly moderate with 62 % followed by low with 19.5 % and high with 18.3 %. Conclusions: the level of total habitual physical activity presented by the students of this educational institution is moderate, which does not meet the recommended levels of physical activity for children and adolescents.

There is a phenotype of obese individuals termed metabolically healthy obese that present a reduced cardiometabolic risk. This phenotype offers a valuable model for investigating the mechanisms connecting obesity and metabolic alterations such as Type 2 Diabetes Mellitus (T2DM). Previously, in an untargeted metabolomics analysis in a cohort of morbidly obese women, we observed a different lipid metabolite pattern between metabolically healthy morbid obese individuals and those with associated T2DM. To validate these findings, we have performed a complementary study of lipidomics. In this study, we assessed a liquid chromatography coupled to a mass spectrometer untargeted lipidomic analysis on serum samples from 209 women, 73 normal-weight women (control group) and 136 morbid obese women. From those, 65 metabolically healthy morbid obese and 71 with associated T2DM. In this work, we find elevated levels of ceramides, sphingomyelins, diacyl and triacylglycerols, fatty acids, and phosphoethanolamines in morbid obese vs normal weight. Conversely, decreased levels of acylcarnitines, bile acids, lyso-phosphatidylcholines, phosphatidylcholines (PC), phosphatidylinositols, and phosphoethanolamine PE (O-38:4) were noted. Furthermore, comparing morbid obese women with T2DM vs metabolically healthy MO, a distinct lipid profile emerged, featuring increased levels of metabolites: deoxycholic acid, diacylglycerol DG (36:2), triacylglycerols, phosphatidylcholines, phosphoethanolamines, phosphatidylinositols, and lyso-phosphatidylinositol LPI (16:0). To conclude, analysing both comparatives, we observed decreased levels of deoxycholic acid, PC (34:3), and PE (O-38:4) in morbid obese women vs normal-weight. Conversely, we found elevated levels of these lipids in morbid obese women with T2DM vs metabolically healthy MO. These profiles of metabolites could be explored for the research as potential markers of metabolic risk of T2DM in morbid obese women.

Inundative biological control (biocontrol) efforts in pest management lead to the mass distribution of commercialized biocontrol agents. Many 'biocontrol gone awry' incidents have resulted in disastrous biodiversity impacts, leading to increased scrutiny of biocontrol efforts. The nematode Phasmarhabditis hermaphrodita is sold as a biocontrol agent on three continents and targets pest gastropods such as Deroceras reticulatum, the Grey Field Slug; P. hermaphrodita is not presently approved for use in the United States. Investigations into the potential for P. hermaphrodita to infect non-target gastropod species of conservation relevance, however, are limited. We examined the effects of three strains of P. hermaphrodita on mortality in Monadenia fidelis, the Pacific Sideband, a snail species endemic to the Pacific Northwest of North America, in laboratory conditions. Across a 71-day laboratory infectivity assay, snails exposed to each of the three nematode strains, each analyzed at two doses, experienced a mean 50% mortality by days 20-42. All nematode-treated snails were dead by the end of the study. By contrast, 30/30 water-control snails experienced no mortality. Nematodes killed smaller, juvenile-stage snails significantly faster than those in larger and more developmentally advanced hosts. Our results provide direct evidence that the biocontrol nematode P. hermaphrodita infects and kills M. fidelis, a non-target gastropod species endemic to the Pacific Northwest, in laboratory conditions. This study suggests that introduction of P. hermaphrodita to new ecosystems might negatively impact endemic gastropod biodiversity and advocates for further investigation of non-target effects, including in conditions closer to the natural environments of non-target species.

Positive-pressure ventilation results in ventilator-induced lung injury, and few therapeutic modalities have been successful at limiting the degree of injury to the lungs. Understanding the primary drivers of ventilator-induced lung injury will aid in the development of specific treatments to ameliorate the progression of this syndrome. There are conflicting data for the role of neutrophils in acute respiratory distress syndrome pathogenesis. Here, we specifically examined the importance of neutrophils as a primary driver of ventilator-induced lung injury in a mouse model known to have impaired ability to recruit neutrophils in previous models of inflammation. We exposed Duoxa+/+ and Duoxa-/- mice to low- or high-tidal volume ventilation with or without positive end-expiratory pressure (PEEP) and recruitment maneuvers for 4 hours. Absolute neutrophils in BAL fluid were significantly reduced in Duoxa-/- mice compared with Duoxa+/+ mice (6.7 cells/μl; 16.4 cells/μl; P = 0.003), consistent with our hypothesis that neutrophil translocation across the capillary endothelium is reduced in the absence of DUOX1 or DUOX2 in response to ventilator-induced lung injury. Reduced lung neutrophilia was not associated with a reduction in overall lung injury in this study, suggesting that neutrophils do not play an important role in early features of acute lung injury. Surprisingly, Duoxa-/- mice exhibited significant hypoxemia, as measured by the arterial oxygen tension/fraction of inspired oxygen ratio and arterial oxygen content, which was out of proportion with that seen in the Duoxa+/+ mice (141, 257, P = 0.012). These findings suggest a role for dual oxidases to limit physiologic impairment during early ventilator-induced lung injury.

Volatile organic compound (VOC) emissions were measured from Chinese Hamster Ovary (CHO) cell and T cell bioreactor gas exhaust lines with the goal of non-invasively metabolically profiling the expansion process. Measurements of cellular 'breath' were made directly from the gas exhaust lines using polydimethylsiloxane (PDMS)-coated magnetic stir bars, which underwent subsequent thermal desorption-gas chromatography-mass spectrometry (TD-GC-MS) analysis. Baseline VOC profiles were observed from bioreactors filled with only liquid media. After inoculation, unique VOC profiles correlated to cell expansion over the course of 8 d. Partial least squares (PLS) regression models were built to predict cell culture density based on VOC profiles of CHO and T cells (R 2 = 0.671 and R 2 = 0.769, respectively, based on a validation data set). T cell runs resulted in 47 compounds relevant to expansion while CHO cell runs resulted in 45 compounds; the 20 most relevant compounds of each cell type were putatively identified. On the final experimental days, sorbent-covered stir bars were placed directly into cell-inoculated media and into media controls. Liquid-based measurements from spent media containing cells could be distinguished from media-only controls, indicating soluble VOCs excreted by the cells during expansion. A PLS-discriminate analysis (PLS-DA) was performed, and 96 compounds differed between T cell-inoculated media and media controls with 72 compounds for CHO cells; the 20 most relevant compounds of each cell line were putatively identified. This work demonstrates that the volatilome of cell cultures can be exploited by chemical detectors in bioreactor gas and liquid waste lines to non-invasively monitor cellular health and could possibly be used to optimize cell expansion conditions 'on-the-fly' with appropriate control loop systems. Although the basis for statistical models included compounds without certain identification, this work provides a foundation for future research of bioreactor emissions. Future studies must move towards identifying relevant compounds for understanding of underlying biochemistry.

The respiratory system is continuously exposed to variety of biological and chemical irritants that contain reactive oxygen species, and these are well known to cause oxidative stress responses in lung epithelial cells. There is a clinical need to identify biomarkers of oxidative stress which could potentially support early indicators of disease and health management. To identify volatile biomarkers of oxidative stress, we analyzed the headspace above human bronchial epithelial cell cultures (HBE1) before and after hydrogen peroxide (H2O2) and cigarette smoke extract (CSE) exposure. Using stir bar and headspace sorptive extraction-gas chromatography-mass spectrometry, we searched for volatile organic compounds (VOC) of these oxidative measures. In the H2O2 cell peroxidation experiments, four different H2O2 concentrations (0.1, 0.5, 10, 50 mM) were applied to the HBE1 cells, and VOCs were collected every 12 h over the time course of 48 h. In the CSE cell peroxidation experiments, four different smoke extract concentrations (0%, 10%, 30%, 60%) were applied to the cells, and VOCs were collected every 12 h over the time course of 48 h. We used partial-least squares (PLS) analysis to identify putative compounds from the mass spectrometry results that highly correlated with the known applied oxidative stress. We observed chemical emissions from the cells that related to both the intensity of the oxidative stress and followed distinct time courses. Additionally, some of these chemicals are aldehydes, which are thought to be non-invasive indicators of oxidative stress in exhaled human breath. Together, these results illustrate a powerful in situ cell culture model of oxidative stress that can be used to explore the putative biological genesis of exhaled breath biomarkers that are often observed in human clinical studies.

Human SCGB1A1 protein has been shown to be significantly reduced in BAL, sputum, and serum from humans with asthma as compared with healthy individuals. However, the mechanism of this reduction and its functional impact have not been entirely elucidated. By mining online datasets, we found that the mRNA of SCGB1A1 was significantly repressed in brushed human airway epithelial cells from individuals with asthma, and this repression appeared to be associated with reduced expression of FOXA2. Consistently, both Scgb1A1 and FoxA2 were downregulated in an ovalbumin-induced mouse model of asthma. Furthermore, compared with wild-type mice, Scgb1a1 knockout mice had increased airway hyperreactivity and inflammation when they were exposed to ovalbumin, confirming the antiinflammatory role of Scgb1a1 in protection against asthma phenotypes. To search for potential asthma-related stimuli of SCGB1A1 repression, we tested T-helper cell type 2 cytokines. Both IL-4 and IL-13 repressed epithelial expression of SCGB1A1 and FOXA2. Importantly, infection of epithelial cells with human rhinovirus similarly reduced expression of these two genes, which suggests that FOXA2 may be the common regulator of SCGB1A1. To establish the causal role of reduced FOXA2 in SCGB1A1 repression, we demonstrated that FOXA2 was required for SCGB1A1 expression at baseline. FOXA2 overexpression was sufficient to drive promoter activity and expression of SCGB1A1 and was also able to restore the repressed SCGB1A1 expression in IL-13-treated or rhinovirus-infected cells. Taken together, these findings suggest that low levels of epithelial SCGB1A1 in asthma are caused by reduced FOXA2 expression.

BackgroundBronchial thermoplasty is a nonpharmacological, device-based treatment option for a specific population of severe asthmatic subjects, but the underlying mechanisms are largely unknown. The purpose of this study is to identify potential altered pathways by bronchial thermoplasty using a transcriptomic approach.MethodsPatients undergoing bronchial thermoplasty were recruited to the study, and a bronchial brushing sample was obtained before each bronchial thermoplasty session and sent for RNA sequencing. A variance component score test was performed to identify those genes whose expression varied after bronchial thermoplasty sessions. Differential gene expression meta-analysis of severe asthmatic subjects versus controls was performed using public repositories. Overlapping genes were included for downstream pathway and network analyses.Results12 patients were enrolled in our study. A total of 133 severe asthma cases and 107 healthy controls from the public repositories were included in the meta-analysis. Comparison of differentially expressed genes from our study patients with the public repositories identified eight overlapping genes: AMIGO2, CBX7, NR3C2, SETBP1, SHANK2, SNTB1, STXBP1 and ZNF853. Network analysis of these overlapping genes identified pathways associated with neurophysiological processes.ConclusionWe have shown that bronchial thermoplasty treatment alters several gene networks that are important in asthma pathogenesis. These results potentially elucidate the disease-modifying mechanisms of bronchial thermoplasty and provide several targets for further investigation.

The use of inhaled, fixed-dose, long-acting muscarinic antagonists (LAMA) combined with long-acting, beta2-adrenergic receptor agonists (LABA) has become a mainstay in the maintenance treatment of chronic obstructive pulmonary disease (COPD). One of the fixed-dose LAMA/LABA combinations is the dry powder inhaler (DPI) of umeclidinium bromide (UMEC) and vilanterol trifenatate (VI) (62.5 µg/25 µg) approved for once-a-day maintenance treatment of COPD. This paper reviews the use of fixed-dose combination LAMA/LABA agents focusing on the UMEC/VI DPI inhaler in the maintenance treatment of COPD. The fixed-dose combination LAMA/LABA inhaler offers a step beyond a single inhaled maintenance agent but is still a single device for the COPD patient having frequent COPD exacerbations and persistent symptoms not well controlled on one agent. Currently available clinical trials suggest that the once-a-day DPI of UMEC/VI is well-tolerated, safe and non-inferior or better than other currently available inhaled fixed-dose LAMA/LABA combinations for COPD.

Objectives: Although only 10% of persons infected with human T-lymphotropic virus type 1 (HTLV-1) may develop virus-associated illnesses over their lifetime, missing the earlier diagnosis of asymptomatic carriers frequently leads to late presentation. Methods: A nationwide HTLV-1 register was created in Spain in 1989. We examined the main demographics and clinical features at the time of the first diagnosis for more than three decades. Results: A total of 428 individuals infected with HTLV-1 had been reported in Spain until the end of 2021. Up to 96 (22%) individuals presented clinically with HTLV-1-associated conditions, including subacute myelopathy (57%), T-cell lymphoma (34%), or Strongyloides stercoralis infestation (8%). Since 2008, HTLV-1 diagnosis has been made at blood banks (44%) or clinics (56%). Native Spaniards and Sub-Saharan Africans are overrepresented among patients presenting with HTLV-1-associated illnesses suggesting that poor epidemiological and/or clinical suspicion, which led to the late presentation are more frequent in them than carriers from Latin America (LATAM) (31.7% vs 20.4%, respectively; P = 0.015). Conclusion: HTLV-1 infection in Spain is frequently diagnosed in patients presenting with characteristic illnesses. Although screening in blood banks mostly identifies asymptomatic carriers from LATAM, a disproportionately high number of Spaniards and Africans are diagnosed too late at the time of clinical manifestations. Expanding testing to all pregnant women and clinics for sexually transmitted infections could help to unveil HTLV-1 asymptomatic carriers.

OBJECTIVES:. To analyze the temporal trend in enrollment rates in a COVID-19 platform trial during the first three waves of the pandemic in the United States. DESIGN:. Secondary analysis of data from the I-SPY COVID randomized controlled trial (RCT). SETTING:. Thirty-one hospitals throughout the United States. PATIENTS:. Patients who were approached, either directly or via a legally authorized representative, for consent and enrollment into the I-SPY COVID RCT. INTERVENTIONS:. None. MEASUREMENTS AND MAIN RESULTS:. Among 1,338 patients approached for the I-SPY COVID trial from July 30, 2020, to February 17, 2022, the number of patients who enrolled (n = 1,063) versus declined participation (n = 275) was used to calculate monthly enrollment rates. Overall, demographic and baseline clinical characteristics were similar between those who enrolled versus declined. Enrollment rates fluctuated over the course of the COVID-19 pandemic, but there were no significant trends over time (Mann-Kendall test, p = 0.21). Enrollment rates were also comparable between vaccinated and unvaccinated patients. In multivariable logistic regression analysis, age, sex, region of residence, COVID-19 severity of illness, and vaccination status were not significantly associated with the decision to decline consent. CONCLUSIONS:. In this secondary analysis of the I-SPY COVID clinical trial, there was no significant association between the enrollment rate and time period or vaccination status among all eligible patients approached for clinical trial participation. Additional studies are needed to better understand whether the COVID-19 pandemic has altered clinical trial participation and to develop strategies for encouraging participation in future COVID-19 and critical care clinical trials.

BackgroundThe aging society posits new socioeconomic challenges to which a potential solution is active and assisted living (AAL) technologies. Visual-based sensing systems are technologically among the most advantageous forms of AAL technologies in providing health and social care; however, they come at the risk of violating rights to privacy. With the immersion of video-based technologies, privacy-preserving smart solutions are being developed; however, the user acceptance research about these developments is not yet being systematized. ObjectiveWith this scoping review, we aimed to gain an overview of existing studies examining the viewpoints of older adults and/or their caregivers on technology acceptance and privacy perceptions, specifically toward video-based AAL technology. MethodsA total of 22 studies were identified with a primary focus on user acceptance and privacy attitudes during a literature search of major databases. Methodological quality assessment and thematic analysis of the selected studies were executed and principal findings are summarized. The PRISMA-ScR (Preferred Reporting Items for Systematic Reviews and Meta-Analyses Extension for Scoping Reviews) guidelines were followed at every step of this scoping review. ResultsAcceptance attitudes toward video-based AAL technologies are rather conditional, and are summarized into five main themes seen from the two end-user perspectives: caregiver and care receiver. With privacy being a major barrier to video-based AAL technologies, security and medical safety were identified as the major benefits across the studies. ConclusionsThis review reveals a very low methodological quality of the empirical studies assessing user acceptance of video-based AAL technologies. We propose that more specific and more end user– and real life–targeting research is needed to assess the acceptance of proposed solutions.

Summary: Background: An urgent need exists to rapidly screen potential therapeutics for severe COVID-19 or other emerging pathogens associated with high morbidity and mortality. Methods: Using an adaptive platform design created to rapidly evaluate investigational agents, hospitalised patients with severe COVID-19 requiring ≥6 L/min oxygen were randomised to either a backbone regimen of dexamethasone and remdesivir alone (controls) or backbone plus one open-label investigational agent. Patients were enrolled to the arms described between July 30, 2020 and June 11, 2021 in 20 medical centres in the United States. The platform contained up to four potentially available investigational agents and controls available for randomisation during a single time-period. The two primary endpoints were time-to-recovery (

In climatically suitable regions across Europe, vineyards can be the dominant perennial crop type. While many wine-growing landscapes are intensively managed, they may still be an attractive habitat for a wide range of bird species. In this study we investigated how breeding birds in three wine-growing regions in Europe (Germany: Palatinate, France: Bordeaux, Austria: Leithaberg) are influenced by the composition of the landscape, focussing on woody semi-natural vegetation. We recorded bird vocalizations with autonomous sound recorders in 93 landscapes across Europe. Bird species were identified according to their songs and calls. The landscape in a 200-m buffer around the recording points was mapped. In total, we recorded 72 bird species, including species typical for vineyard landscapes such as cirl bunting (Emberiza cirlus), hoopoe (Upupa epops) and turtle dove (Streptopelia turtur). For all three countries we found that an increase in overall woody vegetation in the landscape led to an increase in species richness and altered community composition. Most species were recorded in landscapes with abundant hedges, small woods and tree rows rather than in vineyard-dominated landscapes but e.g. woodlark (Lullula arborea) and linnet (Linaria cannabina) showed an opposite preference. We conclude that in intensively used wine-growing landscapes the ongoing decline in farmland birds and the ecosystem services they provide can be reversed by the reintroduction of semi-natural woody vegetation between vineyards. These in frequently many cases linear structural elements can be established included in the landscape with only small losses in production area. [ABSTRACT FROM AUTHOR]

Existen muchas herramientas para desarrollar aplicaciones en Java, pero existen pocas alternativas para framework o bibliotecas especializadas para mostrar gráficos (charts) en entornos web. Aunque la mayoría son para entornos de escritorio, las librerías PrimeFaces y ChartistJSF son una alternativa para la web, pero están orientadas a proyectos basados en Java Server Faces. En este sentido, muchos proyectos prefieren utilizar principalmente una biblioteca de gráficos integrada con JavaScript, lo que implica una curva de aprendizaje adicional y requiere más tiempo en el desarrollo de aplicaciones. Por lo tanto, es necesario tener una biblioteca o marco de visualización de gráficos único para aplicaciones Java en el entorno web. Por lo tanto, en este artículo se propone construir una herramienta que ayude a desarrollar visualizaciones gráficas en proyectos web Java utilizando los conceptos de TagLibs y Webjars. La herramienta propuesta se llama EchartsTag y fue construida siguiendo la metodología XP y validada con SonarQube y un grupo de profesionales expertos en desarrollo de proyectos Java. EchartsTag está disponible en GitHub, por lo que puede ser utilizado por cualquier desarrollador de la comunidad de Java u organizaciones que trabajen con tecnología Java. Finalmente, los resultados de rendimiento de EchartsTag se demuestran al compararlo con otras herramientas alternativas, logrando un tiempo promedio de 14,17 minutos en tiempo de desarrollo y ocupando el tercer lugar en tiempo promedio de visualización que es 3,5 m -después de Chartjs y HighChats. Además, ocupa el primer lugar en la evaluación de otros criterios para el desarrollo web java con herramientas de visualización de gráficos.